Abstract: SA-OR083
Change in Albuminuria and Subsequent Risk of ESRD: A Consortium Meta-Analysis
Session Information
- New Considerations for Renoprotection Clinical Trials
October 27, 2018 | Location: 1B, San Diego Convention Center
Abstract Time: 05:30 PM - 05:42 PM
Category: CKD (Non-Dialysis)
- 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Author
- Coresh, Josef, CKD Prognosis Consortium, Baltimore, Maryland, United States
Group or Team Name
- CKD Prognosis Consortium and CKD Epidemiology Collaboration
Background
A recent NKF-FDA-EMA Workshop evaluated candidate surrogate endpoints for clinical trials to slow kidney disease progression, particularly among participants with relatively preserved baseline glomerular filtration rate (GFR). Here we analyze the strength and consistency of the association between changes in albuminuria and end-stage kidney disease (ESKD) risk across a wide range of cohort studies.
Methods
We included 20 studies with 585,732 individuals and 7,047 ESKD events. Using linear regression of log albuminuria, we quantified the percent change in albuminuria during a baseline period of 1, 2, and 3 years. Associations with subsequent ESKD were quantified using Cox regression in each cohort, followed by random-effects meta-analysis. Further adjustment for regression dilution was used to take into account the high variability of albuminuria to relate risk to true reductions in albuminuria.
Results
Change in urine albumin-to-creatinine ratio (ACR) was strongly related to ESKD risk (Figure). The adjusted hazard ratio of ESKD following a 30% decrease in ACR during a 2-year baseline period was 0.83 (95% CI 0.74-0.94); after further adjustment for regression dilution it was 0.77 (95% CI 0.65-0.92). Adjusted hazard ratios were relatively consistent across subgroups and study types but were somewhat stronger at higher ACR (p-interaction<0.05). Among persons with ACR >300 mg/g, a true reduction in ACR of 30% over 2-years was estimated to confer >1% absolute reduction in 10-year ESKD risk even at preserved GFR (Figure). Results were similar and slightly stronger for PCR.
Conclusion
Change in albuminuria was consistently associated with later risk of ESKD across a wide range of settings lending support to its use as a surrogate endpoint for CKD progression trials. Adjustment for high ACR variability was needed to demonstrate the similar magnitude of observational associations to clinical trials.
Funding
- NIDDK Support